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Background The literature surrounding survival of patients with multiple primary melanomas (MPM) yields variable and opposing findings, constrained by statistical challenges. Objectives To critically examine the available literature regarding survival of patients with MPM compared with a single primary melanoma and detail statistical methods used. Methods Electronic searches were performed of PubMed, Embase, Web of Science, and Scopus, with cross-checking of references, for the period January 1956 to June 2019. Studies published in English examining survival in patients with multiple melanomas were included. Case studies and small case series were excluded. Results There were 14 studies eligible for inclusion. Conclusions on survival varied markedly depending on the statistical method used. Four studies that accounted for survival bias by partitioning the survival time were included in the quantitative review, with 3 of these reporting a survival disadvantage for MPM, whereas the fourth showed no difference in survival. The pooled hazard ratio was 1.39 (95% confidence interval, 1.07-1.81) but with significant heterogeneity (I2 = 96.8%, Phet Limitations Studies showed significant heterogeneity in methodology. Conclusion When data were analyzed with robust statistical methods, patients with MPM had a survival disadvantage compared with patients with a single primary melanoma.